tbuckley/cabot-search huggingface dataset:
Assessment of telehealth experience among a head and neck oncology population.
Authors: Kin Wai (Tony) Hung, Jennifer R. Cracchiolo, Soo Y Kim, Erin F. Gillespie, David G. Pfister
Journal: Journal of Clinical Oncology (2022)

e13650 Background: Studies suggest that oncology patients are satisfied and sometimes prefer telehealth over an in-person visit; however, data are scarce on when patients find telehealth helpful. Such information would be key in understanding how telehealth can be optimally integrated into cancer care delivery. This study aims to identify factors that influence patient experience of telehealth among a multidisciplinary head and neck oncology population. Methods: From Mar 2020 to Dec 2020, we surveyed head and neck oncology patients at a comprehensive cancer center and 6 satellite sites in New York and New Jersey. We assessed patient experience of telehealth versus in-person visit (primary outcome) and their satisfaction with telehealth (secondary outcome). We conducted multivariate regression to analyze covariates that may influence their experience and satisfaction. Covariates included patient factors (age, gender, race, marital status, primary language, home state, home distance from center, current location at home or clinic), clinical factors (diagnosis, performance status, receiving chemotherapy or radiation), physician factors (profession, current location at main or regional campus), visit factors (type, length, billing level, month, first telehealth visit or not), and a technological factor (device type). Results: Among 1,071 completed surveys (response rate 24.0%), 551 first-unique surveys were analyzed. Surveyed patients were predominantly 60 years or older (64.1%), white (88.3%), married (73.8%), and lived within 50 miles from our cancer center (76.1%). Majority had diagnoses of head and neck cancers (65.7%), followed by thyroid cancers (23.8%), and skin cancers (10.5%). While most patients would recommend telehealth (82.4%), only half reported telehealth the same or better compared to in-person visits (55.7%), whereas the other half reported not as good or unsure (44.3%). In multivariate analyses, patients who found telehealth the same or better than in-person visits were more likely to have thyroid cancers (adjusted odds ratios [aOR]: 2.18, CI 95% 1.44 - 3.36) and have visits from July to December (aOR 1.61, CI 95% 1.14 - 2.27). Satisfaction with telehealth was higher among patients with thyroid cancers (aOR: 2.58, CI 95% 1.20 - 6.41), on visits when patients were at home (aOR 3.48, CI 95% 1.37 - 8.42) and when physicians were on campus (aOR 1.73, CI 95% 1.00 - 2.99). Conclusions: Patient experience with telehealth is diverse among the head and neck oncology population; while one-half found telehealth the same or better compared to in-person visits, the other half found it not as good or unsure. More favorable telehealth experience among patient subgroups highlights the multidisciplinary nature of head and neck oncology and improved acceptance of telehealth over time. Future research to optimize patient experience is needed to ensure successful integration of telehealth in head and neck oncology practices.
The distribution of genetic mutations correlated with resistance to KRAS<sup>G12C</sup> inhibitors in Chinese patients with lung cancer.
Authors: Shengcheng Lin, Kai Ma, Yafei Xu, Xinyi Liu, Xiaochun Huang, Mengli Huang
Journal: Journal of Clinical Oncology (2022)

3141 Background: In lung cancer, p.G12C is the most frequent variant in Kirsten rat sarcoma viral oncogene homologue (KRAS) gene. KRAS G12C inhibitors have shown promising efficacy in lung cancer in recent clinical trials, acquired resistance, however, eventually occurred in most patients. Preliminary studies revealed that a number of genetic mutations were correlated with resistance to this type of drugs, including KRAS secondary mutations, KRAS activating mutations, mutations in RTK-RAS-MAPK signaling pathways members, oncogene rearrangements and copy number gain. To clarify the potential clinical application of KRAS G12C inhibitors, herein we analyzed the distribution of reported resistance gene alterations in a large and natural group of Chinese lung cancer, as well as the gene mutation landscape of the subset of patients with suspected resistant mutations. Methods: A total of 32878 Chinese lung cancer including early-stage, late-stage without treatment or late-stage with previously treated were analyzed in this study. Wide NGS panel testing was used to detected single nucleotide variants (SNV), copy number variants (CNV) and oncogenic gene rearrangements. Results: KRAS mutations were detected in 2767 (8.4%) cases, of which KRAS G12C was the most common variant (30.86%). Among 854 patients (2.6%) harbored KRAS G12C, 75 (10%) carried the above resistance mutations, such as G12D/R/V (n = 7). Fusions (20%) which previously observed only in coloretal cancer were unexpectedly detected in this corhort, including EML4-ALK (n = 1), FGFR1-MECOM (n = 1), EWSR1-CHEK2 (n = 2), SPEN-KAZN (n = 2), MET-KCNB2 (n = 1), NOTCH2-NOTCH2NLA (n = 5), SMARCA4-DNAH8 (n = 1), and LIPM-FAS (n = 1). Furthermore, KRAS (46.7%), MYC (25.3%) and MET (10.7%) were amplified. Among this subset of patients with resistant mutations, TP53 (66%), LRP1B (25%), and STK11 (22%) were the most frequently mutated genes. It is noteworthy that STK11/KEAP1 /NFE2L2 gene mutation was detected in nearly 30% in this group of patients. Conclusions: The results of our analysis suggested that about 10% KRAS G12C-mutated Chinese lung cancer patients would be resistant to KRAS G12C inhibitors. Moreover, a small number patients have co-mutated genes which were negatively related to immunotherapy in NSCLC, indicating they were also inappropriate for immunotherapy.
Real-world healthcare resource utilization and costs among patients with multiple myeloma in the United States.
Authors: Niodita Gupta, Ming-Hui Tai, Shuchita Kaila, Philippe Thompson-Leduc, Isabelle Ghelerter, Siyana Kurteva, Patrick Lefebvre, Marie-Hélène Lafeuille
Journal: Journal of Clinical Oncology (2022)

e18811 Background: The economic burden of multiple myeloma (MM) has been shown to increase with more advanced lines of therapy (LOTs). Given the rapidly evolving treatment landscape of MM, this study aimed to describe the current real-world healthcare resource use (HRU) and costs among patients with MM across LOTs. Methods: A commercial insurance claims database was used to identify patients with ≥2 MM diagnoses who initiated a LOT containing an antineoplastic agent for MM between 1/2016 and 2/2021, had continuous insurance coverage ≥6 months before and ≥60 days after first line (1L) initiation, and never received stem cell transplant. LOTs were defined based on agents used within a 60-day period. End of LOT was defined when patients switched treatment, or after a treatment gap of 90 days. HRU and costs (in 2021 USD) were reported for the duration of each LOT (from initiation of LOT to initiation of a subsequent LOT or end of coverage). Results: 1492 patients initiated 1L, 681 initiated 2L, 359 initiated 3L and 188 initiated 4L. Mean age at 1L initiation was 66.6 years. Mean duration of LOT (10.7, 9.4, 8.1 and 10.2 months in 1L, 2L, 3L and 4L, respectively) was longer in 1L than in subsequent LOTs. All-cause monthly outpatient (OP) and inpatient (IP) visits were stable across LOTs (5.0-5.6 OP visits; 0.21-0.32 IP visits). However, mean monthly all-cause costs were lowest in 1L (15.9% - 34.9% lower) as compared to subsequent LOTs ($23.6K in 1L, $29.7K in 2L, $27.3K in 3L and $31.8K in 4L; Table). Conclusions: In this study, the duration of LOT was the longest among 1L patients. Total all-cause healthcare costs were the lowest in 1L than in more advanced LOTs. This suggests that selection of 1L best treatment regimen upfront that prolongs time to disease progression could reduce the overall economic burden of MM.[Table: see text]
Characteristics and clinical outcomes among patients receiving either ibrutinib or anti-CD20 monotherapy as first-line (1L) treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): A retrospective analysis in community oncology practice.
Authors: Julie Vose, Jinghua He, Xiaoxiao Lu, Linda Wu, Tao Ran, Sumeet Panjabi
Journal: Journal of Clinical Oncology (2022)

e19056 Background: Ibrutinib is an oral, once daily Bruton’s tyrosine kinase inhibitor and is a targeted treatment that has demonstrated progression-free survival and overall survival benefits in multiple phase 3 trials across age, fitness, and high-risk markers for CLL/SLL. Despite ibrutinib established as a preferred first-line (1L) treatment option, anti-CD20 monotherapy (rituximab or obinutuzumab) has been prescribed as symptomatic or palliative therapy. This retrospective study compared outcomes between ibrutinib and anti-CD20 monotherapy for CLL/SLL patients who initiated a 1L of therapy in community oncology practice. Methods: The nationwide Flatiron Health Electronic Health Record-derived de-identified database (03/04/2016-08/31/2021) was used to select patients with CLL/SLL who had ≥2 clinic visits and started 1L therapy with ibrutinib or anti-CD20 monotherapy. Patient baseline characteristics prior to 1L initiation were compared between the two treatment groups. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between treatment groups. Kaplan-Meier (KM) analysis was used to evaluate time to next treatment (TTNT) from 1L initiation. Two subgroup analyses were performed among patients with high-risk cytogenetic markers (deletion 17p or 11q, or unmutated IGHV) and those without IGHV testing. Results: Overall, 3,226 patients were included in the analysis, of whom 2,188 (67.8%) received ibrutinib and 1,038 (32.2%) received an anti-CD20 antibody. The average age was 71.4 years for ibrutinib patients and 72.9 years among anti-CD20 users. Patients treated with ibrutinib were more likely to have high-risk cytogenetic markers (42.6% vs 27.9%). Ibrutinib-treated patients overall had a significant 70% risk reduction of initiating a subsequent treatment compared with anti-CD20 group (Table). Similar results were also found in subgroups of patients with high-risk and those without IGHV testing. Conclusions: IPTW-adjusted analysis showed that in the real-world community practice setting, treatment with ibrutinib resulted in a statistically significantly lower risk of initiating subsequent treatment than the anti-CD20 group including patients with high cytogenetic risk features and without IGHV testing.[Table: see text]
Dynamic monitoring circulating tumor DNA in plasma samples by PEAC technology for patients with early-stage non–small cell lung cancer after surgery.
Authors: Ning Li, Bao-Xiao Wang, Wei Ou, Tao Wang, Yue Pu, Teng-Fei Zhu, Xin-Xin Hu, Siyu Wang
Journal: Journal of Clinical Oncology (2022)

8547 Background: Local recurrence or distant metastasis after surgery is not rare for early-stage Non-Small Cell Lung Cancer (NSCLC) patients. Present clinicopathological parameters, such as TNM stages and pathological subtype, are limited effective, as Positive Predictive Value (PPV) is low while Negative Predictive Value (NPV) is high. In recent years, circulating tumor DNA (ctDNA) has emerged as a noninvasive method for early diagnosis, prognostic stratification, disease surveillance, and treatment response evaluation. We assessed whether circulating tumor DNA (ctDNA) detected by PEAC technology could be a biomarker for minimal residual disease (MRD) and prediction of postoperative relapse in early-stage NSCLC. Methods: We enrolled 132 NSCLC patients with EGFR, KRAS, NRAS, BRAF and PIK3CA mutations, and obtained plasma samples at five perioperative time points (before surgery, 3-7 days, 6-months, 12-months and 18-months after surgery). Using PEAC technology, somatic mutations in plasma samples were identified and utilized for ctDNA-based MRD analysis. Clinical follow-ups were collected. Results: Our data showed that 32.0% (8 of 25) of patients with positive preoperative ctDNA experienced postoperative relapse, compared with 7.2% (6 of 83) in ctDNA negative patients, demonstrating that preoperative ctDNA status is an effective prognosis factor for NSCLC. In time point of 3-7 days after surgery, plasma samples were obtained from 47 patients, of which 33.3% (2 of 6) with positive ctDNA experienced postoperative relapse, while only 4.9% (2 of 41) in ctDNA negative patients. The result suggests that ctDNA positive in plasma samples of 3-7 days after surgery might be a strong biomarker for MRD detection and relapse prediction. For ctDNA surveillance, plasma samples from 6-months, 12-months and 18-months after surgery were collected and detected. At any one of the three tests ctDNA is positive, 20.0% (8 of 40) patients experienced clinical relapse, while 5.1% (3 of 59) patients with ctDNA negative status at all times relapse. A total of 14 recurrence events had occurred, ctDNA positivity precedes radiological recurrence by a median of 150.5 days (90.5 – 182, P = 0.006). Conclusions: Perioperative ctDNA analysis using PEAC technology is effective in early detection of MRD and relapse prediction, and hence could benefit NSCLC patient management in clinical settings. Clinical trial information: NCT03465241.
Evaluation of phase 2 single-arm two-stage trials in glioblastoma and brain tumor.
Authors: Wonsuk Yoo, Seongho Kim, Shwetal Mehta, Nader Sanai
Journal: Journal of Clinical Oncology (2022)

e14033 Background: Oncology clinical trials have shown the lowest success rate on Phase 2 and the highest median expense in a new drug to market. We aimed to assess the appropriate implementation of single-arm two-stage Phase 2 trials with other critical design issues of phase 2 single-arm trials such as selection of primary endpoint and historical control rates, and challenges of the blood-brain barrier, and to suggest guidelines to handle design issues related to single-arm Phase 2 trials in Neuro-Oncology. Methods: Two researchers searched with the key words of “phase 2 single arm two-stage design in glioblastoma” through PubMed.gov, clinicaltrials.gov, and Google Scholar to examine study designs of (i) study information, (ii) two-stage design parameters, (iii) rejection numbers and sample size for each stage. Design issues in primary endpoints, historical controls, and challenges on brain tumor trials were discussed with the effect of adaptive design on two-stage designs, and several guidelines on these issues were suggested for investigators in Phase 2 single-arm Neuro-Oncology trials. Results: Almost 50% of single-arm two-stage studies failed to provide key information related to study designs and sample size calculation, even wrong power analysis and interpretation. Response rate and progression-free survival are used as popular surrogate endpoints for overall survival. It is time to evaluate other potential endpoints like post-progress survival and hazard ratio, and usefulness of co-primary endpoint. Investigators should keep transparency of the trials by fully providing and citing historical data source. If there exist large variabilities among existing historical data, meta-analysis can be a good option to accurately estimate the historical control. Conclusions: The appropriate selection on primary endpoint(s) and historical control data, incorporation of adaptive designs if necessary, and right application of two-stage design might help overcoming the challenges on low success rates in new therapeutic oncology trials. Furthermore, the new paradigm of Phase 0 trial might be one potential tool to overcome the challenges with insufficient penetration of therapeutic agents across the blood-brain barrier and limitations in the applicability of animal models to the human condition in glioblastoma and Neuro-Oncology.
Outcomes stratified by molecular aberration following induction with daunorubicin 60 mg/m<sup>2</sup> versus daunorubicin 90 mg/m<sup>2</sup> in AML.
Authors: Keri Renee Maher, Ian Michael Bouligny
Journal: Journal of Clinical Oncology (2022)

e19035 Background: Prior work investigating the optimal dose of daunorubicin in combination with cytarabine for upfront treatment of AML has resulted in several studies suggesting differential responses following daunorubicin dose optimization when analyzed by molecular cohort (such as NPM1, FLT3-ITD, or DNMT3A). While some studies advocated for a dose of 90 mg/m 2 in younger patients with NPM1 mut (following induction with either daunorubicin 45 mg/m 2 versus 90 mg/m 2 ), little is known regarding outcomes stratified by molecular lesion between daunorubicin 60 mg/m 2 and daunorubicin 90 mg/m 2 . Methods: We retrospectively analyzed 92 patients with AML treated with upfront daunorubicin 60 mg/m 2 or 90 mg/m 2 from July 2017 to December 2020 at VCU Massey Cancer Center. Baseline patient demographics were obtained, including cytogenetic risk, molecular profiling either through PCR or NGS at the time of induction, doses of induction regimens, response including MRD analysis (when available), and survival. Results: In the 60 mg/m 2 cohort, 10 patients had NPM1 mut , the CRR (CR+CRi) was 60.0% and the OS was 1.7 y. Four patients with DNMT3 mut had a CRR of 25.0% and a 4.1 m. OS. Nine patients with FLT3-ITD or FLT3-TKD all treated with FLT3 inhibitors achieved a CRR of 22.2% with a 4.9 m. OS. Ten patients with NRAS mut or KRAS mut had a CRR of 50.0% and a 20.7 m. OS. In the adverse category, five with ASXL1 mut had a 20.0% CRR and a 6.4 m. OS; 7 with RUNX1 mut had a CRR of 42.9% and a 14.5 m. OS; and 6 with TP53 mut demonstrated a CRR of 0% and an 13.1 m. OS. In the 90 mg/m 2 cohort, 8 patients had NPM1 mut with a CRR of 75.0% and an 18.8 m. OS. Two patients with DNMT3 mut both achieved CR and the OS was not reached. Three of 5 patients with FLT3 mut treated with midostaurin achieved CR or CRi and a 16.2 m. OS. Four of 5 patients with RAS mut achieved CR and the OS was not reached at a 15.8 m. follow-up time. In the adverse category, there were no patients treated with a dose of 90 mg/m 2 with ASXL1 mut and one with RUNX1 mut with non-evaluable response. Two out of 4 patients achieved CR or CRi with TP53 mut and the OS was not reached. Conclusions: Response rates appear numerically higher across molecular subtypes favoring daunorubicin 90 mg/m 2 , although no significant differences in survival were appreciated, likely due to limited sample size. This may argue for intensification of anthracycline doses in carefully selected patients regardless of molecular profiling. Toxicity with high-dose daunorubicin must be weighed against any potential response or survival benefit, particularly for TP53 mut and ASXL1 mut – especially in the setting of alternative induction strategies such as CPX-351 and venetoclax with a hypomethylating agent. Larger prospective studies analyzing outcomes with regards to molecular profiling and treatment strategies are warranted.
Determination of direct treatment costs of patients with metastatic and nonmetastatic castration-resistant (mCRPC, nmCRPC) and metastatic hormone-sensitive (mHSPC) prostate cancer in Colombia.
Authors: Rafael Niño, Diego Restrepo-Miranda, Miguel Alberto Amezquita, Jeisson Lancheros, Lina Maria Corredor, Yudy Medina, Andres Aguirre
Journal: Journal of Clinical Oncology (2022)

e18838 Background: The purpose of this study was to determine the direct costs associated with the management of patients with metastatic castration resistant (mCRPC), non-metastatic (nmCRPC) and metastatic hormone-sensitive (mHSPC) prostate cancer in the Colombian healthcare system. Methods: First, a literature review was carried out to identify the main clinical recommendations for the treatment and follow-up of patients with prostate cancer at local and international levels. Subsequently, a participation process was developed with clinical experts, through a modified Delphi panel, to validate the natural history of the disease, and identify treatment options, skeletal-related events management, resource utilization, and distribution of patients within stages. Based on the above, a cost analysis model was performed, using Colombian health technology assessment agency recommendations, to calculate direct cost of treatment for mCRPC, nmCRPC and mHSPC from payer’s perspective. Exchange rate used was USD $1 = COP $4,000. Finally, the results were estimated considering the cost per patient per year. Results: According to the cost analysis of each stage, in the non-metastatic castration resistant stage (nmCRPC) the associated yearly cost of a patient was lower than in the metastatic castration resistant stage (mCRPC) (USD $8,581 versus $24,590, respectively), with a difference of USD $16,008. The metastatic hormone-sensitive stage (mHSPC) had a lower yearly cost than the metastatic castration-resistant stage (mCRPC) (USD $15,030 versus $24,590, respectively), with a difference of USD $ 9,559. The event that generated the greatest impact on the cost is the incidence of skeletal-related events associated with disease metastasis (55%). The deterministic sensitivity analysis on key variables, such as the percentage of patients who responded to treatment and the incidence of skeletal-related events, showed consistency of results. Conclusions: Delaying or stopping disease progression to mCRPC could more than halve annual treatment costs for patients. Given the findings, advanced metastatic castration resistant stages demand more resource utilization associated with disease management. The Colombian healthcare system would benefit from risk management strategies that implement timely interventions associated with early diagnosis and screening. In this way, the resource utilization in health sector's institutions would be directly impacted through budget optimization, obtaining better results focused on the national follow-up indicators of the prostate cancer patient cohort.